Hemodynamic Disorders: Edema, Hemorrhage, Thrombosis - PDF

Hemodynamic Disorders Thromboembolic Disease Fundamentals of Pathology 1 Hemodynamic Disorders Thromboembolic Disease and Shock Disorders of Hemodynamics – Edema – Congestion – Shock Hemostasis – Hemorrhage – Thrombosis...

Hemodynamic Disorders Thromboembolic Disease Fundamentals of Pathology 1 Hemodynamic Disorders Thromboembolic Disease and Shock Disorders of Hemodynamics – Edema – Congestion – Shock Hemostasis – Hemorrhage – Thrombosis 2 Hemodynamic Disorders Thromboembolic Disease and Shock Body Fluids and Compartments – 60% of lean body weight is water – Two thirds / intracellular – Remainder / extracellular Interstitium (3rd space) that lies between cells – 5% of total body water is in blood plasma 3 Hemodynamic Disorders Thromboembolic Disease and Shock Fluid Compartments – Interstitial Extracellular 3rd space – Plasma – Intracellular 4 5  Hemodynamic Disorders Thromboembolic Disease and Shock Interstitium RBC o2 H2O H2 O Cells Nutrients Proteins CO2 H2O Lymphatics Lymphatics to Left subclavian vein Capillary / Plasma 6 Hemodynamic Disorders Thromboembolic Disease and Shock Edema – Conditions Resulting in Increased Interstitial Fluid – Increased capillary pressure (Hydrostatic) Impaired venous return – Congestive heart failure – Diminished colloid osmotic pressure – Liver disease – Kidney disease – Malnutrition 7  Conditions Resulting in Increased Interstitial Fluid Increased capillary pressure (Hydrostatic) Diminished colloid osmotic pressure Lack of Perfusion Pressure Lack of Circulating Proteins Proteins lost in urine8 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormal increase in interstitial fluid within tissues – Edema Transudate – Caused by increased hydrostatic pressure or reduced plasma protein – Protein-poor fluid – Heart failure, renal failure, hepatic failure Exudate – Protein-rich fluid – Result of increased vascular permeability (Inflammatory) 9 Hemodynamic Disorders Thromboembolic Disease and Shock Role of Lymphatics 10 Hemodynamic Disorders Thromboembolic Disease and Shock Edema RBC o2 H2 O Cells Nutrients Fluid Proteins CO2 H2O Capillary / Plasma 11 Hemodynamic Disorders Thromboembolic Disease and Shock Role of Lymphatics – Excess extravascular volume Removal Return –via the thoracic duct – Edema Capacity for lymphatic drainage is exceeded 12  Role of Lymphatics Lymphatic fluid flow is from periphery back to the heart 13 Hemodynamic Disorders Thromboembolic Disease and Shock Lymphatic Obstruction – Impairs clearance of interstitial fluid Trauma Invasive tumor Inectious agents – Consequence Lymphedema due to metastatic breast cancer Lymphedema in affected part to axillary nodes and lymphatic obstruction of body Hemodynamic Disorders Thromboembolic Disease and Shock Causes of Edema – Increased hydrostatic pressure Local – Mechanical obstruction to venous drainage Systemic – Cardiac failure results in increased venous pressure – Renal retention of Na+ and water – Decreased Osmotic pressure of plasma Inadequate protein intake – Malnutrition, starvation, malabsorption syndrome Excessive loss – Nephrotic syndrome Reduced synthesis – Liver disease Lymphatic obstruction – Localized lymphedema 15 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Edema – Types Cardiac Edema – Dependent edema – Pitting depressions Renal Edema – Na+ and H2O retention – Generalized (ex.,periorbital edema) Pulmonary Edema – LV failure – Renal failure – Bacterial lung infection may occur Cerebral Edema – Meningitis – Encephalitis 16 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Edema Cardiac Edema – Dependent edema – Pitting depressions 17 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Edema Renal Edema – Generalized (ex.,periorbital edema) 18 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Edema – Cerebral Edema – Trauma – Infection Distended gyri Narrow sulci 19 1. Which of the following is the cause of fluid extravasation outside of pulmonary circulation? A. Increased oncotic pressure B. Increased hydrostatic pressure C. Right heart failure D. Thromboembolus in right ventricle E. Right atrial myxoma 20 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Edema Pulmonary Edema – LV failure – Renal failure Normal CXR – Bacterial lung infection may occur Pulmonary Edema 21 Hemodynamic Disorders Thromboembolic Disease and Shock 22 Hemodynamic Disorders Thromboembolic Disease and Shock 23 Hemodynamic Disorders Thromboembolic Disease and Shock Here’s looking at you kid!! Hmmm…somethings wrong! 24 Hemodynamic Disorders Thromboembolic Disease and Shock Hyperemia – Arteriolar dilation Leads to increased blood flow – Due to inflammation – Skeletal muscle during exercise Affected tissues – Erythematous » 2° to engorgement of vessels with oxygenated blood 25 Hemodynamic Disorders Thromboembolic Disease and Shock Hyperemia – Arteriolar dilation 26 Hemodynamic Disorders Thromboembolic Disease and Shock Congestion – Passive process Caused by reduced outflow of blood from a tissue Can cause edema Lack of blood flow – Chronic hypoxia » Ischemic tissue injury and scarring – Capillary rupture – Catabolism of extravasated RBCs – Hemosiderin-laden macrophages 27 28 Hemodynamic Disorders Thromboembolic Disease and Shock Congestion – Pulmonary congestion – Due to heart failure 29 Hemodynamic Disorders Thromboembolic Disease and Shock Congestion – Pulmonary 30 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Liver 31 32 Hemodynamic Disorders Thromboembolic Disease and Shock Hepatic Congestion (Nutmeg Liver) 33 During an autopsy the following organ was examined from a patient with right heart failure. This organ measured 35cm in greatest dimension. Which of the following description are you going to put on your report regarding this organ? A. Hepatomegaly B. Splenomegaly C. Enlarged Kidney D. Abnormal thymus E. Cardiomegaly 34 Hemodynamic Disorders Thromboembolic Disease and Shock Hemorrhage – Extravasation of blood into the extravascular space Traumatic or non-traumatic 35 Hemodynamic Disorders Thromboembolic Disease and Shock Hemorrhage – Distinct Patterns of Hemorrhage Hematoma Accumulation of Petechiae blood in a body cavity Purpura or location Ecchymoses – Hemothorax – Hemopericardium – Hemoperitoneum – Hemarthrosis – Hematuria 36 Hemodynamic Disorders Thromboembolic Disease and Shock Hemorrhage – Distinct Patterns of Hemorrhage Hematoma Petechiae Purpura Ecchymoses 37 Hemodynamic Disorders Thromboembolic Disease and Shock Hemorrhage – Distinct Patterns of Hemorrhage Accumulation of blood in a body cavity or location – Hemothorax – Hemopericardium – Hemoperitoneum – Hemarthrosis 38 Hemodynamic Disorders Thromboembolic Disease and Shock 33 yo man with multiple hemorrhagic liver cyst Clinical Presentation – Hemoperitoneum – Case Rupture of hemorrhagic cyst 39 Hemodynamic Disorders Thromboembolic Disease and Shock 62 yo man with chronic untreated hypertension Clinical Presentation – Intracerebral hemorrhage 40 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis 41 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Sequence of events at sites of vascular injury Involves – Vascular wall (Endothelium) – Platelets – Coagulation cascade 42  Hemodynamic Disorders Thromboembolic Disease and Shock Review of Vascular Morphology Vascular wall (Endothelium) 43  Review of Vascular Morphology Know the layers and associated structures 44 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Coagulation Cascade 45  Normal Hemostasis – Sequence of events at site of vascular injury  Normal Hemostasis – Sequence of events at site of vascular injury  Platelet Receptors Deficiency – Bernard – Soulier Deficiency - Syndrome Glanzmann Trombasthenia Injury Site vWF stimulates platelet adhesion to subendothelial collagen via GpIb receptors on platelets 48 Hemodynamic Disorders Thromboembolic Disease and Shock Platelet to Platelet Adherence – Mediated by fibrinogen via GpII/IIIa receptors 49 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Sequence of events at site of vascular injury Vascular injury Arteriolar vasoconstriction (endothelin) Subendothelial ECM exposed (vonWillebrand Factor) Platelet adherence and activation (TXA2) Platelet activation and platelet aggregation (Hemostatic plug) Tissue factor is also exposed (FIII / thromboplastin) FIII + FVII initiates coagulation cascade Thrombin generation Thrombin cleaves fibrinogen into insoluble fibrin Fibrin meshwork 50 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Prothrombotic Properties Platelet adherence – Mediated by von Willebrand factor (vWF) » Cofactor for platelet binding to matrix elements » GpIb receptors for vWF » GpIIb-IIIa receptors for fibrinogen Tissue factor – Synthesized by endothelial cells » Stimulated by IL-1, TNF, bacterial endotoxins (sepsis) Tissue Plasminogen activator (t-PA) – Synthesized by endothelial cells » Limits hemostatic plug 51 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Coagulation Cascade Series of enzymatic conversions Inactive proenzymes are activated Result is thrombin formation Thrombin converts fibrinogen into fibrin monomers Fibrin gel encases platelets Hemostatic plug 52 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Coagulation Cascade 53 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Actions of Thrombin (FII) Platelet aggregation Endothelial activation Lymphocyte activation Monocyte activation Fibirn formation 54 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Pathology Lab – Laboratory Assessment of Coagulation Cascade – Light Blue-Top Tube (Sodium Citrate) – Lavender-Top Tube (EDTA) 55 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Coagulation Cascade Clinical Pathology Lab – Extrinsic Pathway » Prothrombin time (PT) » Assesses function of FVII, X, II, V, and fibrinogen (2 5 7 10 fibrinogen) 56 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Coagulation Cascade 57 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Coagulation Cascade Clinical Pathology Lab – Intrinsic Pathway » Partial thromboplastin time (PTT) » Assesses function of FXII, XI, IX, VIII (8 9 11 12) 58 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Coagulation Cascade 59 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Coagulation Cascade Clinical Pathology Lab – Special Note – Vit K dependent factors » Factors II, VII, IX, X – Vit K cofactor in glutamic acid residue carboxylation » Necessary for calcium binding » Antagonized by coumadin Proteins C and S (Vitamin K dependent) – Inactivates factors Va and VIIIa 60 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis – Thrombosis Inhibitors (Clot control) Antithrombin III – Inhibits thrombin, (9, 10,11, 12 – active forms) Proteins C and S – Inactivates factors Va and VIIIa 61 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis and control of clot formation Clot Control – Antithrombin III – Thrombin 62 1 63 Hemodynamic Disorders Thromboembolic Disease and Shock Restricting Coagulation – Fibrinolysis Plasmin – Breaks down fibrin preventing polymerization – Fibrin split products (FSPs) are produced – D-dimers 64 Hemodynamic Disorders Thromboembolic Disease and Shock Restricting Coagulation – Fibrinolysis Elevated levels of FD/SPs and D-dimers – Disseminated intravascular coagulation (DIC) – Deep vein thrombosis (DVT) – Pulmonary embolism (PE) 65 Hemodynamic Disorders Thromboembolic Disease and Shock Restricting Coagulation Fibrinolysis – Plasmin Breaks down fibrin preventing polymerization D-dimers Fibrin split products 66 Restricting Coagulation / Fibrinolysis 67 Factors Facilitating and Associated with Thrombosis Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Endothelial Injury Physical loss of endothelium – Exposure of the subendothelial ECM » Trauma » Transmural infarction (Heart) Endothelial cell dysfunction – Perturbation in prothombotic and antithrombotic activities » Bacterial endotoxins » Radiation injury 69 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Alterations in Blood Flow Turbulence – Endothelial cell injury » Valular vegetations » Atherosclerotic plaques » Aneurysms » Hypertension Interruption of Laminar Flow – Stasis (Heart failure, vascular obstruction) » Promotes endothelial cell activation » Concentrates coagulation factors » Platelet contact to endothelium 70 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Alterations in Blood Flow Turbulence – Valular vegetations » Interfere with laminar flow of blood 71 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Alterations in Blood Flow Turbulence – Atherosclerotic plaques 72 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Alterations in Blood Flow Turbulence – Aneurysms 73 Hemodynamic Disorders Thromboembolic Disease and Shock Coagulation Disorders 74 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Hypercoagulability of the Blood Primary (Genetic) Disorders – Factor V mutation (Leiden mutation) » Mutation renders factor V resistant to cleavage by protein C – Mutations in prothrombin gene – Elevations of Homocysteine 75 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Hypercoagulability of the Blood Secondary (Acquired) Disorders – Heparin-induced thrombocytopenia (HIT) syndrome » Heparin induced Ab synthesis against platelets – Antiphospholipid Antibody Syndrome » Autoantibodies activates platelets – Paradox » Promotes thrombosis in vivo » Prolongs clotting time (PPT) in vitro 76 Hemodynamic Disorders Thromboembolic Disease and Shock Case #68217 29 yo with difficulty breathing and right leg pain Concerned about miscarriage in previous pregnancy G2P1 0 1 1 Labs –  Platelets – PTT > 70 (n=30sec) 77 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Hypercoagulability of the Blood Antiphospholipid Antibody Syndrome – Clinical Presentations » Recurrent thromboses » Repeated miscarriages » Cardiac valve vegetations » Thrombocytopenia » Pulmonary embolism 78 Hemodynamic Disorders Thromboembolic Disease and Shock Case # 5682 Patient is a 34 yo woman with recurrent deep vein thrombosis (DVT) Laboratory studies reveal mild prolongation of PT and PTT 79  Oral Contraceptives  Synthesis of Coagulation Factors  Anticoagulant Synthesis 80 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Clot Control – Antithrombin III – Thrombin 81 Hemodynamic Disorders Thromboembolic Disease and Shock Normal Hemostasis Coagulation Cascade 82 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Hypercoagulability of the Blood Disseminated Cancers – Release of procoagulant tumor products 83 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Characteristics Sites of Thrombi Arterial or cardiac thrombi – Sites of turbulence or endothelial injury – Grow in retrograde fashion Venous thrombi – Sites of stasis – Extend in the direction of blood flow Thrombi can embolize (Thromboemboli) 84 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Morphology of Thrombi Contain Laminations – Lines of Zahn » Alternating platelet and fibrin / RBCs Arterial thrombi are occlusive Venous thrombosis (Phlebothrombosis) – Red, or stasis, thrombi – Veins of the lower extremities most commonly involved 85 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Morphology of Thrombi Lines of Zahn 86 Hemodynamic Disorders Thromboembolic Disease and Shock Abnormalities Associated with Thrombosis – Dynamic changes Involving Thrombi Propagation Embolization Dissolution Organization and recanalization 87 Dynamic changes involving Thrombi 88 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Thrombi – Venous Thrombosis Saphenous veins (seen in varicosities) stasis Deep venous thrombosis (DVT) – Associations Hypercoagulable States (bed rest and immobilization) – CHF – Trauma, surgery, and burns – Pregnancy (associated with hypercoagulability ) – Tumor-associated inflammation and tumor antigens » Migratory thrombophlebitis or Trousseau syndrome 89 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Thrombi – Arterial and Cardiac Thrombosis Atherosclerosis – Endothelial injury Cardiac mural thrombi – Post MI (Endothelial injury) Aortic / mural thrombi can embolize – Distal organs and tissues affected 90 Hemodynamic Disorders Thromboembolic Disease and Shock Clinical Consequences of Thrombi – Cardiac mural thrombi Injury to endothelial cells that can occur with MI’s – Aortic / mural thrombi can embolize 91 Hemodynamic Disorders Thromboembolic Disease and Shock Disseminated Intravascular Coagulation (DIC) 92 Hemodynamic Disorders Thromboembolic Disease and Shock Disseminated Intravascular Coagulation – Characteristics – Widespread fibrin thrombi in the microcirculation (widespread activation of thrombin) – Widespread microvascular thrombosis – Platelet and coagulation protein consumption – Activation of fibrinolytic pathways – Bleeding catastrophe 93 Disseminated Intravascular Coagulation 94 Hemodynamic Disorders Thromboembolic Disease and Shock Conditions Precipitating DIC Obstetric complications Advanced malignancy Massive trauma Sepsis Burns (significant area of body) 95 Hemodynamic Disorders Thromboembolic Disease and Shock Disseminated Intravascular Coagulation – Laboratory Diagnosis Fibrin degradation / split products (D-dimers) Fragmented RBCs on blood smear Prolonged Bleeding Time / Prothrombin Time  Fibrinogen  Platelets  FDPs 96 Hemodynamic Disorders Thromboembolic Disease and Shock Disseminated Intravascular Coagulation – Laboratory Diagnosis Fragmented RBCs on blood smear Shistocytes 97 Hemodynamic Disorders Thromboembolic Disease and Shock Embolism – Intravascular Solid Liquid Gas Silicone??? – Carried from point A B distant from its point of origin Vessel caliber accommodation 98 Hemodynamic Disorders Thromboembolic Disease and Shock – Types Pulmonary Emboli – Originate from leg DVTs – Saddle embolus / sudden death Small Medium size Emboli – Clinically silent – Chest pain – Hemoptysis – Chronic cor pulmonale – Pulmonary hypertension (PHT) 99 Hemodynamic Disorders Thromboembolic Disease and Shock Pulmonary Emboli – Originate from deep vein thromboses (DVTs) above knee – Homans Sign 100 Hemodynamic Disorders Thromboembolic Disease and Shock Pulmonary Emboli – Large emboli block bifurcation of pulmonary artery Saddle Embolus – Right heart failure (acute cor pulmonale) – Sudden death 101 Hemodynamic Disorders Thromboembolic Disease and Shock Systemic Thromboemboli – Emboli of Arterial Origin Intracardiac mural thrombi – Left ventricular wall infarcts – Left atrial dilation and fibrillation Aortic aneurysms Ulcerated atherosclerotic plaques Valvular vegetation Paradoxical emboli 102  Hemodynamic Disorders Thromboembolic Disease and Shock Systemic Thromboemboli – Emboli of Arterial Origin Intracardiac mural thrombi Left ventricular wall infarcts Aortic aneurysms Dilated cardiomyopathy 103 Hemodynamic Disorders Thromboembolic Disease and Shock Systemic Thromboemboli – Emboli of Arterial Origin Aortic aneurysms – Infarction of distal extremities 104 Hemodynamic Disorders Thromboembolic Disease and Shock Systemic Thromboemboli – Venous Emboli (Sources) Fat and Marrow Embolus Air / Gas Embolus Amniotic Fluid Embolus Silicone 105 Hemodynamic Disorders Thromboembolic Disease Systemic Thromboemboli – Venous Emboli (Sources) Fat and Marrow Fat and Marrow Embolus Embolus Amniotic Fluid Embolus Silicone Amniotic Fluid Embolus 106 Hemodynamic Disorders Thromboembolic Disease and Shock Infarction – Area of Ischemic Necrosis Primary causes – Vascular occlusion » Arterial » Venous 107 Hemodynamic Disorders Thromboembolic Disease and Shock – Factors That Influence Infarct Development Nature of the vascular supply Rate at which an occlusion develops Vulnerability to hypoxia Oxygen content of the blood 108 Hemodynamic Disorders Thromboembolic Disease and Shock – Organs and Tissues affected by Infarction – Heart – Brain – Lungs – GI / SLI – Distal extremities 109 Hemodynamic Disorders Thromboembolic Disease and Shock – Morphology of Infarcts Red Infarcts – Occur with venous occlusions » (e.g., testicular torsion) – In loose, spongy tissues » (e.g., lung) where blood can collect in the infarcted zone – In tissues with dual circulations » (e.g., lung and small intestine) that allow blood to flow from an unobstructed parallel supply into a necrotic zone) – In tissues previously congested by sluggish venous outflow 110 Hemodynamic Disorders Thromboembolic Disease and Shock – Morphology of Infarcts Red Infarcts – Tissues with dual circulations – Wedge-shaped (ex. Lung infarct) Lung 111 Whoops and OUCH!!!! 112 Hemodynamic Disorders Thromboembolic Disease and Shock – Morphology of Infarcts Red Infarcts – Venous occlusions Testicular torsion 113 Hemodynamic Disorders Thromboembolic Disease and Shock – Morphology of Infarcts White Infarcts – Occur with arterial occlusions in solid organs with end- arterial circulation » (e.g., heart, spleen, and kidney) – Where tissue density limits the seepage of blood from adjoining capillary beds into the necrotic area. 114 Hemodynamic Disorders Thromboembolic Disease and Shock – Morphology of Infarcts White Infarcts – Solid organs with end- arterial circulation Spleen 115 Hemodynamic Disorders Thromboembolic Disease and Shock Morphological Characteristics – Ischemic coagulative necrosis Replaced by scar – Liquefactive necrosis Cystic cavity remains 116 Disintegration of the Persistence of Memory Salvador Dali 117 1931